SP-SAP, a conjugate between the peptide neurotransmitter substance P, and the ribosome-inactivating protein, saporin, has been shown, through previous NIH funding, to ablate chronic pain transmission in several rat models. Importantly, acute, reflexive pain perception remains intact. The conjugate acts by elimination of the small number of substance P receptor-expressing neurons in the superficial laminae of the dorsal horn of the spinal cord after intrathecal injection. The Food and Drug Administration has recommended that the initial patient population for this drug be terminal cancer patients in pain that is refractory to opioids. The purpose of this application is to obtain funding to move this drug closer to clinical trial by establishing Good Manufacturing Practice (GMP)-grade SP-SAP and by taking SP-SAP through toxicology/safety studies in the rat and the dog, as requested by the FDA. Funding is requested for equipment to complete a GMP-level facility, for synthesis of SP-SAP for toxicology/safety (not at GMP level), for the actual toxicology/safety studies (that will be sub-contracted) and for the preparation of protocols that satisfy the FDA request for GMP materials. Finally, GMP-grade SP-SAP will be synthesized in preparation for clinical trial.